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Central insulin dysregulation in antipsychotic-naïve first-episode psychosis: In silico exploration of gene expression signatures.
Lee, Jiwon; Xue, Xiangning; Au, Emily; McIntyre, William B; Asgariroozbehani, Roshanak; Tseng, George C; Papoulias, Maria; Panganiban, Kristoffer; Agarwal, Sri Mahavir; Mccullumsmith, Robert; Freyberg, Zachary; Logan, Ryan W; Hahn, Margaret K.
Afiliación
  • Lee J; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Electronic address: jiwonlee.lee@mail.utoronto.ca.
  • Xue X; Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States. Electronic address: xix66@pitt.edu.
  • Au E; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. Electronic address: e.au@mail.utoronto.ca.
  • McIntyre WB; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: brett.mcintyre@mail.utoronto.ca.
  • Asgariroozbehani R; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Electronic address: roshanak.asgariroozbehani@mail.utoronto.ca.
  • Tseng GC; Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States. Electronic address: ctseng@pitt.edu.
  • Papoulias M; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Electronic address: maria.papoulias@camh.ca.
  • Panganiban K; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Electronic address: kris.panganiban@mail.utoronto.ca.
  • Agarwal SM; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address: mahavir.agarwal@camh.ca.
  • Mccullumsmith R; Department of Neurosciences, University of Toledo, Toledo, Ohio, United States; ProMedica, Toledo, Ohio, United States. Electronic address: robert.mccullumsmith@utoledo.edu.
  • Freyberg Z; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, United States; Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States. Electronic address: freyberg@pitt.edu.
  • Logan RW; Department of Psychiatry, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States; Department of Neurobiology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States. Electronic address: ryan.logan@umassmed.edu.
  • Hahn MK; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address: margaret.hahn@camh.ca.
Psychiatry Res ; 331: 115636, 2024 Jan.
Article en En | MEDLINE | ID: mdl-38104424
ABSTRACT
Antipsychotic drug (AP)-naïve first-episode psychosis (FEP) patients display premorbid cognitive dysfunctions and dysglycemia. Brain insulin resistance may link metabolic and cognitive disorders in humans. This suggests that central insulin dysregulation represents a component of the pathophysiology of psychosis spectrum disorders (PSDs). Nonetheless, the links between central insulin dysregulation, dysglycemia, and cognitive deficits in PSDs are poorly understood. We investigated whether AP-naïve FEP patients share overlapping brain gene expression signatures with central insulin perturbation (CIP) in rodent models. We systematically compiled and meta-analyzed peripheral transcriptomic datasets of AP-naïve FEP patients along with hypothalamic and hippocampal datasets of CIP rodent models to identify common transcriptomic signatures. The common signatures were used for pathway analysis and to identify potential drug treatments with discordant (reverse) signatures. AP-naïve FEP and CIP (hypothalamus and hippocampus) shared 111 and 346 common signatures respectively, which were associated with pathways related to inflammation, endoplasmic reticulum stress, and neuroplasticity. Twenty-two potential drug treatments were identified, including antidiabetic agents. The pathobiology of PSDs may include central insulin dysregulation, which contribute to dysglycemia and cognitive dysfunction independently of AP treatment. The identified treatments may be tested in early psychosis patients to determine if dysglycemia and cognitive deficits can be mitigated.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastornos Psicóticos / Antipsicóticos / Resistencia a la Insulina Límite: Humans Idioma: En Revista: Psychiatry Res Año: 2024 Tipo del documento: Article Pais de publicación: Irlanda

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastornos Psicóticos / Antipsicóticos / Resistencia a la Insulina Límite: Humans Idioma: En Revista: Psychiatry Res Año: 2024 Tipo del documento: Article Pais de publicación: Irlanda